TY - JOUR
T1 - Leukemia-associated genetic aberrations in mesenchymal stem cells of children with acute lymphoblastic leukemia
AU - Shalapour, Shabnam
AU - Eckert, Cornelia
AU - Seeger, Karl
AU - Pfau, Madlen
AU - Prada, Javier
AU - Henze, Günter
AU - Blankenstein, Thomas
AU - Kammertoens, Thomas
N1 - Funding Information:
Acknowledgments The authors are grateful to S. Tuerkmen for metaphase analysis and M. Nagy for chimerism analysis and to R. Marschalek for MLL sequence analysis. We thank the staff members of the ALL-REZ BFM study group, Shidokht Shalapour, T. Schüler, and L. Bastian for their support. This work was supported by the DFG Sonderforschungsbereich TR 36 and the Deutsche Krebshilfe (Bonn, Germany).
PY - 2010/3
Y1 - 2010/3
N2 - Childhood acute lymphoblastic leukemia (ALL) is caused by malignant immature lymphocytes. Even though childhood ALL can be cured in a large number of patients, around 20% of the patients suffer a relapse after chemotherapy. The origin of the relapse is unclear at the present time. Given the high plasticity of cells, we searched for leukemia-associated genetic aberrations and immunoglobulin (IG) gene rearrangements in mesenchymal stem cells (MSC) from childhood B-cell precursor ALL patients. MSC from all ten ALL patients analyzed presented the chromosomal translocations that had been detected in leukemia cells (TEL-AML1, E2A-PBX1, or MLL rearrangement). The proportions of translocation-positive MSC varied between 10% and 54% depending on the patients and the time point of analysis. Leukemia-specific IG gene rearrangements were detected in the MSC from three ALL patients. The detection of leukemia-associated genetic aberrations in MSC indicates a clonal relationship between MSC and leukemia cells and suggests their involvement in the pathogenesis and/or pathophysiology of childhood ALL.
AB - Childhood acute lymphoblastic leukemia (ALL) is caused by malignant immature lymphocytes. Even though childhood ALL can be cured in a large number of patients, around 20% of the patients suffer a relapse after chemotherapy. The origin of the relapse is unclear at the present time. Given the high plasticity of cells, we searched for leukemia-associated genetic aberrations and immunoglobulin (IG) gene rearrangements in mesenchymal stem cells (MSC) from childhood B-cell precursor ALL patients. MSC from all ten ALL patients analyzed presented the chromosomal translocations that had been detected in leukemia cells (TEL-AML1, E2A-PBX1, or MLL rearrangement). The proportions of translocation-positive MSC varied between 10% and 54% depending on the patients and the time point of analysis. Leukemia-specific IG gene rearrangements were detected in the MSC from three ALL patients. The detection of leukemia-associated genetic aberrations in MSC indicates a clonal relationship between MSC and leukemia cells and suggests their involvement in the pathogenesis and/or pathophysiology of childhood ALL.
KW - Childhood acute lymphoblastic leukemia
KW - Chromosomal translocations
KW - Fusion genes
KW - IG gene rearrangements
KW - Mesenchymal stem cells
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U2 - 10.1007/s00109-009-0583-8
DO - 10.1007/s00109-009-0583-8
M3 - Article
C2 - 20155409
AN - SCOPUS:77449131485
SN - 0946-2716
VL - 88
SP - 249
EP - 265
JO - Journal of Molecular Medicine
JF - Journal of Molecular Medicine
IS - 3
ER -